ENPL_MOUSE
ID ENPL_MOUSE Reviewed; 802 AA.
AC P08113; P11427;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Endoplasmin;
DE AltName: Full=94 kDa glucose-regulated protein;
DE Short=GRP-94;
DE AltName: Full=Endoplasmic reticulum resident protein 99 {ECO:0000303|PubMed:3036833};
DE Short=ERp99 {ECO:0000303|PubMed:3036833};
DE AltName: Full=Heat shock protein 90 kDa beta member 1;
DE AltName: Full=Polymorphic tumor rejection antigen 1;
DE AltName: Full=Tumor rejection antigen gp96;
DE Flags: Precursor;
GN Name=Hsp90b1; Synonyms=Grp94, Tra-1, Tra1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3036833; DOI=10.1016/s0021-9258(18)47496-0;
RA Mazzarella R.A., Green M.;
RT "ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum,
RT is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa
RT glucose regulated protein (GRP94).";
RL J. Biol. Chem. 262:8875-8883(1987).
RN [2]
RP PROTEIN SEQUENCE OF 76-84; 88-95; 117-135; 143-156; 244-265; 270-285;
RP 385-404; 416-428; 435-448; 512-530; 609-623 AND 640-660, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 378-507.
RX PubMed=3612811; DOI=10.1016/0022-2836(87)90381-0;
RA Smith M.J., Koch G.L.E.;
RT "Isolation and identification of partial cDNA clones for endoplasmin, the
RT major glycoprotein of mammalian endoplasmic reticulum.";
RL J. Mol. Biol. 194:345-347(1987).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-88.
RX PubMed=2438686; DOI=10.1073/pnas.84.11.3807;
RA Srivastava P.K., Chen Y.-T., Old L.J.;
RT "5'-structural analysis of genes encoding polymorphic antigens of
RT chemically induced tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:3807-3811(1987).
RN [5]
RP PROTEIN SEQUENCE OF 271-284; 328-339 AND 633-659.
RX PubMed=2768254; DOI=10.1016/s0021-9258(18)63814-1;
RA Koyasu S., Nishida E., Miyata Y., Sakai H., Yahara I.;
RT "HSP100, a 100-kDa heat shock protein, is a Ca2+-calmodulin-regulated
RT actin-binding protein.";
RL J. Biol. Chem. 264:15083-15087(1989).
RN [6]
RP INTERCHAIN DISULFIDE BOND, AND GLYCOSYLATION.
RX PubMed=8179819; DOI=10.1089/dna.1994.13.117;
RA Qu D., Mazzarella R.A., Green M.;
RT "Analysis of the structure and synthesis of GRP94, an abundant stress
RT protein of the endoplasmic reticulum.";
RL DNA Cell Biol. 13:117-124(1994).
RN [7]
RP COMPONENT OF A CHAPERONE COMPLEX.
RX PubMed=12475965; DOI=10.1091/mbc.e02-05-0311;
RA Meunier L., Usherwood Y.-K., Chung K.T., Hendershot L.M.;
RT "A subset of chaperones and folding enzymes form multiprotein complexes in
RT endoplasmic reticulum to bind nascent proteins.";
RL Mol. Biol. Cell 13:4456-4469(2002).
RN [8]
RP IDENTIFICATION IN AN EIF2 COMPLEX WITH EIF2S1; EIF2S2; CELF1; CALR3; HSPA5
RP AND CALR.
RX PubMed=16931514; DOI=10.1074/jbc.m605701200;
RA Timchenko L.T., Salisbury E., Wang G.-L., Nguyen H., Albrecht J.H.,
RA Hershey J.W., Timchenko N.A.;
RT "Age-specific CUGBP1-eIF2 complex increases translation of CCAAT/enhancer-
RT binding protein beta in old liver.";
RL J. Biol. Chem. 281:32806-32819(2006).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP INTERACTION WITH MZB1.
RX PubMed=21093319; DOI=10.1016/j.immuni.2010.11.013;
RA Flach H., Rosenbaum M., Duchniewicz M., Kim S., Zhang S.L., Cahalan M.D.,
RA Mittler G., Grosschedl R.;
RT "Mzb1 protein regulates calcium homeostasis, antibody secretion, and
RT integrin activation in innate-like B cells.";
RL Immunity 33:723-735(2010).
RN [11]
RP FUNCTION, INTERACTION WITH CNPY3; TLR4; TLR9 AND TLR11, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF GLU-103.
RX PubMed=20865800; DOI=10.1038/ncomms1070;
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA Bona R., Han D., Li Z.;
RT "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a
RT substrate-specific cochaperone.";
RL Nat. Commun. 1:79-79(2010).
RN [12]
RP ERRATUM OF PUBMED:20865800.
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA Bona R., Han D., Li Z.;
RL Nat. Commun. 3:653-653(2012).
RN [13]
RP INTERACTION WITH AIMP1.
RX PubMed=17525271; DOI=10.2353/ajpath.2007.061266;
RA Han J.M., Park S.G., Liu B., Park B.-J., Kim J.Y., Jin C.H., Song Y.W.,
RA Li Z., Kim S.;
RT "Aminoacyl-tRNA synthetase-interacting multifunctional protein 1/p43
RT controls endoplasmic reticulum retention of heat shock protein gp96: its
RT pathological implications in lupus-like autoimmune diseases.";
RL Am. J. Pathol. 170:2042-2054(2007).
RN [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-217.
RX PubMed=19349973; DOI=10.1038/nbt.1532;
RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M.,
RA Schiess R., Aebersold R., Watts J.D.;
RT "Mass-spectrometric identification and relative quantification of N-linked
RT cell surface glycoproteins.";
RL Nat. Biotechnol. 27:378-386(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-479, SUCCINYLATION [LARGE SCALE
RP ANALYSIS] AT LYS-404 AND LYS-633, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Molecular chaperone that functions in the processing and
CC transport of secreted proteins (PubMed:20865800). When associated with
CC CNPY3, required for proper folding of Toll-like receptors
CC (PubMed:20865800). Functions in endoplasmic reticulum associated
CC degradation (ERAD) (By similarity). Has ATPase activity
CC (PubMed:20865800). May participate in the unfolding of cytosolic
CC leaderless cargos (lacking the secretion signal sequence) such as the
CC interleukin 1/IL-1 to facilitate their translocation into the ERGIC
CC (endoplasmic reticulum-Golgi intermediate compartment) and secretion;
CC the translocation process is mediated by the cargo receptor TMED10 (By
CC similarity). {ECO:0000250|UniProtKB:P14625,
CC ECO:0000269|PubMed:20865800}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Component of an EIF2 complex at
CC least composed of CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1
CC and HSPA5. Part of a large chaperone multiprotein complex comprising
CC DNAJB11, HSP90B1, HSPA5, HYOU, PDIA2, PDIA4, PDIA6, PPIB, SDF2L1, UGGT1
CC and very small amounts of ERP29, but not, or at very low levels, CALR
CC nor CANX. Interacts with OS9 (By similarity). Interacts with AIMP1;
CC regulates its retention in the endoplasmic reticulum. Interacts with
CC CNPY3; this interaction is disrupted in the presence of ATP. Interacts
CC with TLR4, TLR9 and TLR11, but not with TLR3. Interacts with MZB1 in a
CC calcium-dependent manner. Interacts with METTL23 (By similarity).
CC Interacts with IL1B; the interaction facilitates cargo translocation
CC into the ERGIC (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P14625}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum lumen
CC {ECO:0000269|PubMed:20865800}. Sarcoplasmic reticulum lumen
CC {ECO:0000250|UniProtKB:P41148}. Melanosome
CC {ECO:0000250|UniProtKB:P14625}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:8179819}.
CC -!- SIMILARITY: Belongs to the heat shock protein 90 family. {ECO:0000305}.
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DR EMBL; J03297; AAA37573.1; -; mRNA.
DR EMBL; M29652; AAA37743.1; -; mRNA.
DR EMBL; M16370; AAA40023.1; -; mRNA.
DR CCDS; CCDS36019.1; -.
DR PIR; A29317; A29317.
DR RefSeq; NP_035761.1; NM_011631.1.
DR AlphaFoldDB; P08113; -.
DR SMR; P08113; -.
DR BioGRID; 204301; 43.
DR CORUM; P08113; -.
DR DIP; DIP-32352N; -.
DR IntAct; P08113; 16.
DR MINT; P08113; -.
DR STRING; 10090.ENSMUSP00000020238; -.
DR ChEMBL; CHEMBL3425396; -.
DR GlyConnect; 2287; 14 N-Linked glycans (4 sites).
DR GlyGen; P08113; 6 sites, 14 N-linked glycans (4 sites).
DR iPTMnet; P08113; -.
DR PhosphoSitePlus; P08113; -.
DR SwissPalm; P08113; -.
DR REPRODUCTION-2DPAGE; P08113; -.
DR SWISS-2DPAGE; P08113; -.
DR EPD; P08113; -.
DR jPOST; P08113; -.
DR PaxDb; P08113; -.
DR PeptideAtlas; P08113; -.
DR PRIDE; P08113; -.
DR ProteomicsDB; 275868; -.
DR ABCD; P08113; 3 sequenced antibodies.
DR Antibodypedia; 1290; 1381 antibodies from 49 providers.
DR DNASU; 22027; -.
DR Ensembl; ENSMUST00000020238; ENSMUSP00000020238; ENSMUSG00000020048.
DR GeneID; 22027; -.
DR KEGG; mmu:22027; -.
DR UCSC; uc007gqi.1; mouse.
DR CTD; 7184; -.
DR MGI; MGI:98817; Hsp90b1.
DR VEuPathDB; HostDB:ENSMUSG00000020048; -.
DR eggNOG; KOG0020; Eukaryota.
DR GeneTree; ENSGT01020000230401; -.
DR HOGENOM; CLU_006684_1_3_1; -.
DR InParanoid; P08113; -.
DR OMA; KVSKTTW; -.
DR OrthoDB; 924636at2759; -.
DR PhylomeDB; P08113; -.
DR TreeFam; TF105969; -.
DR Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-MMU-3000480; Scavenging by Class A Receptors.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-6785807; Interleukin-4 and Interleukin-13 signaling.
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 22027; 18 hits in 74 CRISPR screens.
DR ChiTaRS; Hsp90b1; mouse.
DR PRO; PR:P08113; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P08113; protein.
DR Bgee; ENSMUSG00000020048; Expressed in embryonic post-anal tail and 249 other tissues.
DR ExpressionAtlas; P08113; baseline and differential.
DR Genevisible; P08113; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0034663; C:endoplasmic reticulum chaperone complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0033018; C:sarcoplasmic reticulum lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005790; C:smooth endoplasmic reticulum; ISO:MGI.
DR GO; GO:0097524; C:sperm plasma membrane; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0031247; P:actin rod assembly; ISO:MGI.
DR GO; GO:0071318; P:cellular response to ATP; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IBA:GO_Central.
DR GO; GO:0043666; P:regulation of phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0030970; P:retrograde protein transport, ER to cytosol; IEA:Ensembl.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; ISS:UniProtKB.
DR Gene3D; 1.20.120.790; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR HAMAP; MF_00505; HSP90; 1.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR019805; Heat_shock_protein_90_CS.
DR InterPro; IPR037196; HSP90_C.
DR InterPro; IPR001404; Hsp90_fam.
DR InterPro; IPR020575; Hsp90_N.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR PANTHER; PTHR11528; PTHR11528; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF00183; HSP90; 1.
DR PIRSF; PIRSF002583; Hsp90; 1.
DR PRINTS; PR00775; HEATSHOCK90.
DR SMART; SM00387; HATPase_c; 1.
DR SUPFAM; SSF110942; SSF110942; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR PROSITE; PS00014; ER_TARGET; 1.
DR PROSITE; PS00298; HSP90; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Calcium; Chaperone; Direct protein sequencing;
KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydroxylation;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Sarcoplasmic reticulum; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..802
FT /note="Endoplasmin"
FT /id="PRO_0000013599"
FT REGION 290..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 749..802
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 799..802
FT /note="Prevents secretion from ER"
FT COMPBIAS 290..314
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 753..802
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 107
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41148"
FT BINDING 149
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41148"
FT BINDING 162
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41148"
FT BINDING 199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41148"
FT SITE 448
FT /note="Important for ATP hydrolysis"
FT /evidence="ECO:0000250|UniProtKB:P41148"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14625"
FT MOD_RES 168
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000250|UniProtKB:P14625"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66HD0"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14625"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q66HD0"
FT MOD_RES 404
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P14625"
FT MOD_RES 479
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 633
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 785
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P14625"
FT CARBOHYD 62
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 217
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19349973"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 481
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 502
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 138
FT /note="Interchain"
FT MUTAGEN 103
FT /note="E->A: Loss of CNPY3-binding."
FT /evidence="ECO:0000269|PubMed:20865800"
SQ SEQUENCE 802 AA; 92476 MW; BDF33B9BD86BFC5F CRC64;
MRVLWVLGLC CVLLTFGFVR ADDEVDVDGT VEEDLGKSRE GSRTDDEVVQ REEEAIQLDG
LNASQIRELR EKSEKFAFQA EVNRMMKLII NSLYKNKEIF LRELISNASD ALDKIRLISL
TDENALAGNE ELTVKIKCDK EKNLLHVTDT GVGMTREELV KNLGTIAKSG TSEFLNKMTE
AQEDGQSTSE LIGQFGVGFY SAFLVADKVI VTSKHNNDTQ HIWESDSNEF SVIADPRGNT
LGRGTTITLV LKEEASDYLE LDTIKNLVRK YSQFINFPIY VWSSKTETVE EPLEEDEAAK
EEKEESDDEA AVEEEEEEKK PKTKKVEKTV WDWELMNDIK PIWQRPSKEV EEDEYKAFYK
SFSKESDDPM AYIHFTAEGE VTFKSILFVP TSAPRGLFDE YGSKKSDYIK LYVRRVFITD
DFHDMMPKYL NFVKGVVDSD DLPLNVSRET LQQHKLLKVI RKKLVRKTLD MIKKIADEKY
NDTFWKEFGT NIKLGVIEDH SNRTRLAKLL RFQSSHHSTD ITSLDQYVER MKEKQDKIYF
MAGSSRKEAE SSPFVERLLK KGYEVIYLTE PVDEYCIQAL PEFDGKRFQN VAKEGVKFDE
SEKTKESREA TEKEFEPLLN WMKDKALKDK IEKAVVSQRL TESPCALVAS QYGWSGNMER
IMKAQAYQTG KDISTNYYAS QKKTFEINPR HPLIRDMLRR IKEDEDDKTV MDLAVVLFET
ATLRSGYLLP DTKAYGDRIE RMLRLSLNID PEAQVEEEPE EEPEDTSEDA EDSEQDEGEE
MDAGTEEEEE ETEKESTEKD EL
